Saudi Cultural Missions Theses & Dissertations
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Item Restricted A probabilistic modelling framework for generalising the cause-and-effect relationships of the toxic cyanobacterium Lyngbya majuscula's harmful algal blooms in Moreton Bay, Queensland, Australia(The University of Queensland, 2024-06-04) Al Saeed, Abdullateef; Pullar, David; Johnstone, RonThe increase of harmful algal blooms (HABs) in estuaries and coastal waters is a global concern for ecological, economic, and health reasons. As such, there is a need to develop suitable management strategies based on an understanding of algal blooms’ cause-and-effect relationships. Extant studies have significantly improved our understanding of the eutrophication processes that trigger HABs in various environments. However, Moreton Bay in Australia is a complex estuarine system, with inflows from major rivers, tidal flows, and an ocean barrier of islands and sand bars. Such biophysical and spatial features lead to significant variability in the ecosystem which makes it difficult to generalise such cause-effect relationships. This has raised debate among scientific communities about bloom initiation and development which, in turn, has obstructed appropriate management planning. Moreton Bay has been subject to HABs of the cyanobacterium Lyngbya majuscula with confounding causes since the late 1990s. There is still no certainty about whether naturally driven factors, human-related changes, or a combination of both are underpinning the frequency and expansion of L. majuscula blooms and distribution in Moreton Bay. Despite efforts to model and predict the initiation of L. majuscula, scientific explanations on the cause-and-effect relationships have had limited success. While extant models have considered significant environmental and socioeconomic factors, variables influencing the generic occurrence of hypoxia (depleted dissolved oxygen (DO) concentration below 3 mg/L) have yet to be thoroughly incorporated due, in part, to insufficient monitoring data collected on DO and chlorophyll-a (chl-a). Moreover, the relationship between L. majuscula’s preferred habitat and the ability of benthic sediments to induce hypoxia and provide bioavailable nutrients for initiation and growth has not been investigated. This thesis adopts the hypothesis that hypoxic water conditions at the benthos are an essential cause of L. majuscula initiation, specifically when bioavailable nutrients are concomitantly released from the sediments to the water column. Such processes may be described in terms of spatial-temporal patterns and may be statistically generalised by probabilistic models to distinguish influential factors in the initiation and occurrence of L. majuscula in Moreton Bay. These models may also provide the ability to identify locations under threat of experiencing HABs.4 0Item Restricted Regulation of the carotid body type-1 cell by lipid signalling pathways(University of Oxford, 2024-02-09) Alsahafi, Zaki; Buckler, Keith; Pandit, JaideepDespite several proposed theories, the precise mechanism underlying acute oxygen sensing in type-1 cells of the carotid body remains elusive. This thesis investigates the role of Gq- coupled receptors and PLC signalling molecules in the regulation of carotid body type-1 cells by utilizing Ca2+ measurements and single channel electrophysiology. This thesis investigates the involvement of these signalling molecules in hypoxia-induced [Ca2+]i rise and TASK channel inhibition in type-1 cells. In addition, this thesis examines the role of PLC signalling molecules in mediating the effects of metabolic poisons and volatile anaesthetics on TASK channels in type-1 cells. This thesis seeks to address the question as to whether there might be a common signalling pathway mediating all these effects. Specifically, it proposes that lipid signalling may ultimately be central to all these forms of TASK channel regulation. Following the general introduction and methods chapters, chapter 3 examines the effects of Gq- coupled receptors and PLC signalling molecules on the hypoxia-induced [Ca2+]i rise in type-1 cell. The results show that hypoxia-induced [Ca2+]i rise was sensitive to alterations in Gq-coupled receptors and PLC-signalling molecules, suggesting that these signalling molecules are involved in mediating the hypoxia-induced [Ca2+]i rise in type-1 cells. Chapter 4, further examines the role of these signalling molecules by looking at their effects on the activity of TASK channels in type-1 cells. This chapter presents novel findings demonstrating the involvement of PLC signalling molecules in mediating the hypoxic inhibition of TASK channels in type 1 cells. It proposes a model for acute oxygen sensing in these cells, incorporating findings from chapters 3 and 4. Chapter 5 examines the role of PLC signalling molecules in mediating the effects of metabolic inhibitors on TASK channels. Metabolic inhibitors are known to inhibit TASK channels in type-1 cells and other cell types. We further confirmed this and showed that these effects are not likely to be mediated by PLC-produced DAG. Chapter 6 examines the interactions between DAG and halothane on TASK channels in type-1 cells. We demonstrated that DiC8, a DAG analogue, induced a strong, reversible, and dose-dependent inhibition of TASK channels and inhibited the halothane-induced activation of these channels. These novel findings support the hypothesis that anaesthetics and endogenous ligands may compete for binding sites in sensitive proteins. In conclusion, this thesis presents novel findings on the role of Gq-coupled receptors and PLC signalling molecules in the regulation of carotid body type-1 cells and suggests that these signalling molecules are involved in mediating the responses of type-1 cells to various endogenous and exogenous stimuli. Additionally, it posits that PLC signalling molecules establish a connection between metabolic function and the modulation of TASK channels by hypoxia in type-1 cells.30 0Item Restricted Advancing Osteoarthritis Care: Unlocking Potential with DMOG and Hyaluronic Acid Treatment(Saudi Digital Library, 2023-11-21) Mortada, Hassan; Gentelmen, EileenOsteoarthritis is a common temporomandibular disease among the adults. Characterized by continues degeneration of chondrocytes which results to altered joint structure and function. The leading approach to cater this issue is to stimulate the regeneration of chondrocytes. In our study we are aiming to stimulate chondrogenesis via a drug called Dimethyl oxalyl glycine associated with Hyaluronic acid gel encapsulating exosomes. Dmog is a Prolyl Hydroxylase inhibitor this mechanism is crucial due to stabilizing hypoxia inducible factor. Prolyl hydroxylase inhibits HIF-1 Alpha. Thus, Dmog stabilizes HIF-1 alpha which results to regulation of chondrocytes genes, increase protein release, and regeneration. Hyaluronic acid (HA) is a naturally occurring polysaccharide that is widely studied for its biological and biomedical applications. Hyaluronic acid will degrade over time which will allow DMOG to gradually stimulate into the targeted site delivered by exosomes. The concentration of hyaluronic acid is crucial for a gradual release of Dmog. Understanding the relationship between concentration and absorbance is vital for accurate quantification and characterization of HA, as well as for evaluating its behavior encapsulating cells, exosomes, and therapeutical drugs. This study aims to investigate the concentration-absorbance relationship of HA through the construction of a standard curve using known concentrations of fluorescent and carbazole assay. It also evaluates chondrocytes gene expressions via QPCR and Immunostaining for protein release and founding that Dmog drug and hypoxic environments are beneficial to induce chondrocyte proliferation and regeneration. The experiment involved four different groups, each consisting of samples with varying concentrations of HA encapsulating mainly 1% and 2%. Also,100nm and 200nm on each concentration respectively. Fluorescent beads mimics the sizes of exosomes used in active practice are encapsulated inside the Hyaluronic acid hydrogels. The carbazole assay was employed to determine the degradation period corresponding to different HA concentrations over a period of time. A series of standard solutions with known concentrations of HA were prepared and subjected to spectrophotometric analysis. The absorbance of each standard solution was measured at a specific wavelength, and a calibration curve was constructed by plotting absorbance against concentration. The resulting standard curve served as a reference to determine the concentration of unknown HA samples based on their absorbance values. Statistical analysis was performed to assess the accuracy and reliability of the method, including the calculation of regression parameters and determination of coefficient of determination (R²) values. In addition, we experimented chondrocytes behaviors under Dmog and Hypoxic environments to evaluate genes expression regulation under physiological hypoxia and chemical hypoxia compared to untreated group. Physiological hypoxia cells were preserved in 5% CO2 hypoxia cabinets, chemical hypoxia had Dmog mixed with media 6% CO2, and the untreated samples had a normal oxygen levels 20% CO2. QPCR provided an insight into genes expression, which could enhance Chondrogenesis. Immunostaining was employed to determine Aggrecan, Col I, and Col II, which are important proteins for Chondrocytes proliferation.In the result, The key findings of the experiments on the relationship between concentration and absorbance in Hyaluronic acid degradation process. The results were visualized using a standard curve. Also, beads release into the supernatant were evaluated using fluorescence assay. Fluorescence beads were used to mimic exosomes in this study used common sizes of exosomes were used 100nm and 200nm. The results clearly demonstrate the observed patterns that suggested 2% concentration of Hyaluronic acid has the optimal potential for a slow degradation rate (7) days, highlighting the importance of understanding the concentration-absorbance relationship in Hyaluronic acid analysis. These findings contribute to our understanding of Hyaluronic acid behavior and its potential applications in various fields. Also, The key findings of QPCR and immunostaining is it provided a positive results and Chondrogenesis responsible genes are elevated while being under Dmog drug and Hypoxic condition compared to Control (untreated) conditions.39 0